Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients

Abstract

Bacterial communities in the airways of cystic fibrosis (CF) patients are, as in other ecological niches, influenced by autogenic and allogenic factors. However, our understanding of microbial colonization in younger versus older CF airways and the association with pulmonary function is rudimentary at best. Using a phylogenetic microarray, we examine the airway microbiota in age stratified CF patients ranging from neonates (9 months) to adults (72 years). From a cohort of clinically stable patients, we demonstrate that older CF patients who exhibit poorer pulmonary function possess more uneven, phylogenetically-clustered airway communities, compared to younger patients. Using longitudinal samples collected form a subset of these patients a pattern of initial bacterial community diversification was observed in younger patients compared with a progressive loss of diversity over time in older patients. We describe in detail the distinct bacterial community profiles associated with young and old CF patients with a particular focus on the differences between respective "early" and "late" colonizing organisms. Finally we assess the influence of Cystic Fibrosis Transmembrane Regulator (CFTR) mutation on bacterial abundance and identify genotype-specific communities involving members of the Pseudomonadaceae, Xanthomonadaceae, Moraxellaceae and Enterobacteriaceae amongst others. Data presented here provides insights into the CF airway microbiota, including initial diversification events in younger patients and establishment of specialized communities of pathogens associated with poor pulmonary function in older patient populations.

Figure 1. Patient age is related to pulmonary function and aspects of community relatedness.

Boxplots with age bins containing three or more samples are displayed; Relationships between patient age and (A) pulmonary function (B) Net Relatedness Index and (C) Nearest Taxon Index are illustrated. As pulmonary function declines, increasing phylogenetic relatedness at both the deeper levels and terminal branches of the phylogenetic tree respectively is evident.

Figure 2. Phylogenetic tree displaying relationship between patient age and taxon abundance.

Taxa exhibiting a significant increase (red) or decrease (blue) in relative abundance with increasing CF patient age are illustrated. Scale bar indicates 0.01 nucleotide substitutions per base.

Figure 3. Bacterial community structure and composition associated with CF patient age.

Compared to pediatric communities, adult CF patient airway communities exhibit lower bacterial diversity and are more uneven. Increased diversity in younger airways is correlated with a large number of known pathogenic families. Loss of diversity in older airways is strongly correlated with loss of pulmonary function and emergence of competitively dominant species such as members of the Pseudomonadacece, Burkholderiaceae and Xanthomonadaceae. For simplicity, the initial increase in diversity exhibited by younger CF patients is not illustrated.